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Publication numberUS3646059 A
Publication typeGrant
Publication dateFeb 29, 1972
Filing dateMay 5, 1969
Priority dateMay 5, 1969
Publication numberUS 3646059 A, US 3646059A, US-A-3646059, US3646059 A, US3646059A
InventorsRichard K Brantley
Original AssigneeDu Pont
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Plant growth regulatory ureidopyrazoles
US 3646059 A
Abstract  available in
Images(7)
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Claims  available in
Description  (OCR text may contain errors)

. o a 3,646,059 Umted States Patent @ffice 1 wherein: PLANT GROw i gi IigEGULATORY R is hydrogen, methyl, ethyl, or phenyl;

R 1 1, 1, IDOP ZOLES 1 1s cyc ohexy pheny or Richard K. Brantley, Wilmington, DeL, assignor to E. I.

du Pont de Nemours and Company, Wilmington, Del. 5 No Drawing. Filed May 5, 1969, Ser. No. 822,001

Int. Cl. C07d 49/20 US. or. 260-310 R 3 Claims C? B ABSTRACT OF THE DISCLOSURE Certain ureidopyrazoles, such as (i) 5-(3-phenylureido)l,3-dimethylpyrazole or (ii) 5-[3-(2-fluorophenyl) ureido]-4-chloro-1,3-dimethylpyrazole, have been found to fl nl be effective as plant growth modifiers. The ureidopyrazoles hydrogen, fiuofo, bfOmO, or y and are particularly useful as defoliants on cotton, soybean, B 18 hydfogfin, of nitro;

and dry bean plants. R is hydrogen or methyl;

X is hydrogen, methyl, brorno, or chloro; and Y is methyl or ethyl, DES RI T ON THE N EN ON 20 C P I OF I V TI and to the use of said compounds as plant growth modi Summary fiers. This invention is directed to compounds having the for- P ed compounds are mula: dimethylpyrazole and 5-[3-(2-fluorophenyl)ureido]-4- R chloro-1,3-dimethylpyrazole. R1 0 H N l| N Method for preparing compounds i The compounds of this invention can be prepared ac- X Y cording to the following exemplary reaction schemes:

I l M I c CN Na CH 2 on on RNHWHQ ij M: *2 a N c I 1 1 E E3 CH3 O H X2 R n x N N-C-N ZR NCO N g 1 i .l

Reaction Scheme 3.

React-ion Scheme 2 Dimerization of a nitrile leads to the formation of an aminonitrile. The nitrile can be dimerized by using methods well known in the art. These methods generally consist of heating the nitrile with or without a solvent in the presence of a strongly alkaline material. Preferred alkalis are alkali and alkaline earth metals as Well as their hy drides and alkoxides. The aminonitrile is recovered from the reaction mixture by acidification, filtration, and distillation. The preparation of the aminopyrazole can be carried out by heating the aminonitrile and substituted hydrazine to a temperature of from 50 C. to 150 C. in the presence of a solvent, such as ethyl alcohol. At this point, halogenation of the 4-position may be performed by reacting the aminopyrazole with a halogenating agent, such as bromine or sulfuryl chloride, in the presence of a solvent, such as water, acetic acid, or carbon tetrachloride, and optionally an acid acceptor, such as sodium acetate or sodium carbonate. The halogenated or non-halogenated aminopyrazoles can be reacted with either an organic monoisocyanate, an N-(hydrocarbyl)carbamoyl halide, or an N,N-di(hydrocarbyl)carbamoy1 halide. The reaction of the aminopyrazole and isocyanate readily occurs in a non-polar solvent, such as benzene. A catalytic amount of a tertiary amine, such as triethylamine, often is desirable to catalyze the reaction. The reaction of the aminopyrazole and the carbamoyl halide occurs in an inert solvent, such as benzene. The presence of an acid acceptor in the reaction mixture is desirable. Suitable acid acceptors include tertiary amines, such as pyridine, or an excess of the aminopyrazole. The ureidopyrazole can be recovered by stripping off the solvent and recrystallization of the residue. The halogenation of the 4-position can be carried out subsequent to the reaction of the aminopyrazole and the isocyanate or carbamoyl halide in the same manner as the aminopyrazole.

The compounds of this invention can be considered to be substituted ureas. When R is not hydrogen, the portion of the molecule which contains R and R is derived from an N,N-di(hydrocarbyl)carbamoyl halide. When R is hydrogen, the R portion of the molecule is derived from an isocyanate.

The following examples illustrate the preparation of the compounds of this invention. Unless otherwise stated, parts are parts by weight.

EXAMPLE 1 Preparation of S-amino-1,3-dirnethylpyrazole Eight and two-tenths parts of B-aminocrotonitrile and 4.5 parts of methylhydrazine are dissolved in 100 parts of ethanol and boiled under reflux for 12 hours. The mixture is then subjected to distillation at reduced pressure. The fraction which has a boiling point of 155 C. at 32 mm. Hg. absolute is 5-arnino-l,3-dimethylpyrazole. When this HZNT l to.

An equivalent amount of hydrazine can be substituted for the methylhydrazine used in the procedure of Example 1. This substitution will yield 5-amino-3-methylpyrazole. Likewise the substitution of ethylhydrazine and phenylhydrazine in the procedure of Example 1 will lead to the formation of 5 amino-l-ethyl-3-methylpyrazole and 5- amino-1-phenyl-3-methylpyrazole, respectively.

The above mentioned pyrazoles can be reacted with isocyanates according to the procedures of Examples 3 or 8, infra, to give appropriate ureidopyrazoles. Thus, if 5-amino-3-methylpyrazole is reacted with phenyl isocyanate or cyclohexyl isocyanate the respective products will be 5-(3-phenylureido)-3 methylpyrazole and 5-(3-cyclohexylureido -3 -methylpyrazole.

Dimerization of propionitrile will yield 2 cyano-3- amino-2-pentene. When an equivalent amount of this material is used in place of fi-aminocrotonitrile in the procedure of Example 1, 5-amino-3-ethyl-1,4-dimethylpyrazole will be produced. This pyrazole can be reacted with an isocyanate according to the procedures of Example 3 or 8, infra. If the isocyanate is phenyl isocyanate, the product will be 5-(3-phenylureido)-3-ethyl-1,4-dimethylpyrazole.

EXAMPLE 2 Preparation of 5-amino-4-bromo-1,3-dimethylpyrazole Eleven and one-tenths parts of 5-amino-l,3-dimethylpyrazole is dissolved in a mixture of parts of acetic acid and 10 parts of sodium acetate. Thereafter, 16 parts of bromine is added slowly to the solution while maintaining good agitation. After the bromine addition is complete, the material is poured onto about 300 parts of crushed ice. The mixture is made slightly alkaline with aqueous ammonia and there extracted with methylene chloride. Upon drying with anhydrous magnesium sulfate and removal of the solvent under reduced pressure, 5-amino-4-bromo-l,3-dimethylpyrazole is recovered as a heavy oil. The compound has the following structure:

LOH.

EXAMPLE 3 Preparation of 5-(3-phenylureido)-4-bromo-1,3-

dimethylpyrazole EXAMPLES 4-7 The following isocyanates when substituted in the amounts indicated for phenyl isocyanate in the procedure of Example 3 react to give the product indicated.

6 EXAMPLE 8 Preparation of 5-(3-cyclohexylureido)-1,3-dimethylpyrazole Three and three tenths parts of 5-amino-1,3-dimethylpyrazole is dissolved in 50 parts of benzene. Three and eight tenths parts of cyclohexyl isocyanate is added and the mixture warmed on a steam bath for one hour. Upon l0 cooling and addition of n-hexane, solids form which are collected by filtration and purified by recrystallization from acetonitrile. The product has a melting point of 196 C. and the following structure:

Example Isoeyanate Parts Product 4 P-Chlorophenylisocyannte 2.5 O H (FH;

11 N c1--Nc-N- l H B1CH;;

5 [3-(t-chloropheuyl)ureido]-4-br0mo-1,3-dimathylpyrazolo 5 o-Bromopheuylisocyanate 2.7 Br CH Ii F r:

A Q l 0 N Br "*CIIQ 5-[3-(2-bromophenyl)ureid01-4-bromo-1,3-dimcthylpyrazole 6 o-Fluorophenylisocyanate 2.2 P O H $11 u N @r f N Br-- CHa 5-[3-(2-fluor0pheny1)ureid0]-4-bromo-1,3-dimethylpyrazole 7 r. p-tolylisocynnate 2.2 CH

it l

Br- -CH 5-(3-p-tolylureido)-4-br0mo-1,3-dimethylpyrazole EXAMPLES 9-12 The following isocyanates when substituted in the amounts indicated for cyclohexyl isocyanate in the procedure of Example 8 react to give the product indicated.

Example Isocyanate Parts Product 9 o-Fluoro henylisocyanate 4.0 F CH t It C? t 6 W N 5-[3-(2-Iluorophenyl)ureido]-l,3-dimethylpyrazolo 10 3,4-dieh1orophenylisoeyanate 5.7 Cl OH;

i i N Q 1 \N I H I Tim.

543-(3,4-diehlorophenydl)ureido]-1,3-dimethylpyra2olo Example Isocyanate Parts Product 11 m-Nitrophenyl isocyanate 5. 1 N C O H (I311;

l N 'w \N l H I S-[E-(E-nitrophenyl) ureldol-l,3-dimethylpyrazole 12.-.. o-Bromophenyl isocyanate. 6. Br CH EXAMPLE 13 Preparation of -[3- (2-fluorophenyl)ureido]-1,3-

dimethyl-4-chloropyrazole Six parts of 5-[3-(2-fiuorophenyl)ureido]-l,3-dimethylpyrazole is dissolved in a warm solution of 4 parts of sodium acetate and 200 parts of acetic acid. Three and one-half parts of sulfuryl chloride is added to the solution which is then agitated for minutes. The mixture is poured into 500 parts of ice water. Precipitated solids are collected by filtration and recrystallization from methanol. The recovered compound has a melting point of 210 C. and the following structure:

t H i EXAMPLE 14 Preparation of 5-(3-rnethyl-3-phenyl-ureido)- 1,3-dimethylpyrazole Eleven and one-tenth parts of 5-aminol,3-dimethylpyrazole is dissolved in a mixture of 200 parts of benzene and 10 parts of pyridine. Seventeen parts of N-methyl-N- phenylcarbamoyl chloride is added and the resulting mixture agitated and boiled under reflux for one hour. The mixture is then cooled and washed in order with (i) a l N sodium hydroxide solution, (ii) 1 N hydrochloric acid, and (iii) water. After drying with anhydrous magnesium sulfate and evaporation of the solvent, a good grade of crude subject compound remains. The pure compound has the following structure:

UTILITY The compounds of this invention are useful as plant defoliants and accordingly can be used to cause the leaves to drop from numerous plants. This ability to cause leaves to drop is most useful on plants such as cotton, soybeans, seed alfalfa, and dry beans before harvest. The com- 7 pounds also retard the rate of regrowth of the defoliated plants.

The amount of compound required for optimum effects will depend on the particular crop and environment under which it is growing. Within the meaning of this case, the amount of compound necessary to accomplish defoliation will be termed an effective amount. Normally, the rate at which the compound is applied will range from 0.10 to 15.0 kilogram per hectare. One skilled in the art will be able to select the appropriate rate of application for any particular situation.

5-{3-(2-bromophenyl)ureidol-l,S-dlrnethylpyrazole Compositions The compounds of the present invention can be used in the form of compositions which are prepared by admixing at least one of the active compounds with an inert diluent, such as pest control adjuvants or modifiers, to provide compositions in the form of dusts, water-dispersible powders, high-strength concentrates, and aqueous or organic dispersions. Thus, the compounds of this invention can be used with a carrier or diluent agent such as a finely divided solid, an organic liquid, water, a wetting agent, a dispersing agent, an emulsifying agent, or any suitable combination of these.

The compositions, especially liquids and wettable powders, may contain as a conditioning agent one or more surface-active agents, sometimes called surfactants, in amounts suflicient to render a given composition containing the compounds of this invention readily dispersible in water or in oil.

The surface-active agent used in this invention can be a wetting, dispersing, or an emulsifying agent which will assist dispersion of the compound. The surface-active agent can include such anionic, cationic, and nonionic agents as have heretofore been generally employed in plant control compositions of similar type. Suitable surface-active agents are set forth, for example, in Detergents and Ernulsifiers" 1968 Annual by John W. McCutcheon, Inc.

In general, less than 10% by weight of the surfaceactive agent will be used in compositions of this invention and ordinarily the amount of surface-active agents will range from 1% to 5% but may even be less than 1% by weight.

Additional surface-active agents can be added to the formulations to increase the ratio of surfactant to active ingredient up to as high as 5 to 1 by weight. Such com positions have a greater regulatory effectiveness than can be expected from a consideration of the activity of the components used separately. When used at higher rates it is preferred that the surfactant be present in the range of one-fifth to live parts surfactant for each one part of active agent.

(A) Wettable powders Wettable powders are water-dispersible compositions containing the active material, an inert solid extender, and one or more surfactants to provide rapid wetting and prevent heavy flocculation when suspended in water.

The inert extenders which are preferred for use in the wettable powders of this invention containing the active compounds are of mineral origin.

The classes of extenders suitable for the wettable powder formulations of this invention are the natural clays, diatornaceous earth, and synthetic mineral fillers derived from silica and silicate. Most preferred fillers for this invention are kaolinites, attapulgite clay, montmoriflonite clays, synthetic silicas, synthetic magnesium silicate, and calcium sulfate dihydrate.

Suitable surfactants for use in such compositions are those listed in Detergents and Emulsifiers 1968 Annual by J. W. McCutcheon, Inc. Among the more preferred surfactants are the non-ionic and anionic type, and those most suitable for the preparation of the dry, wettable products of this invention are solid forms of compounds known to the art as wetters and dispersants. Occasionally a liquid, non-ionic compound classified primarily as an emulsifier may serve as both wetter and dispersant.

Most preferred wetting agents are alkylbenzeneand alkylnaphthalenesulfonates; sulfated fatty alcohols, longchain acid esters of sodium isethionate; esters of sodium sulfosuccinate; sulfated or sulfonated fatty acid esters; petroleum sulfonates; sulfonated vegetable oils; and ditertiary acetylenic glycols. Preferred dispersants are methylcellulose, polyvinyl alcohol, lignin sulfonates, polymeric alkylnaphthalenesulfonates, polymethylene bisnaphthalenesulfonate, and sodium N-methyl-N-(long chain acid)taurates.

Wetting and dispersing agents in these preferred wettable powder compositions of this invention are usually present at concentrations of from about 0.5 weight percent to weight percent. The inert extender then completes the formulation. Where needed, 0.1 weight percent to 1.0 weight percent of the extender may be replaced by a corrosion inhibitor or an anti-foaming agent or both.

Thus, wettable powder formulations of the invention will usually contain from about 25 to 90 weight percent active material, from 0.5 to 2.0 weight percent wetting agent, from 0.25 to 5.0 weight percent dispersant, and from 9.25 to 74.25 weight percent inert extender, as these terms are described above.

When the wettable powder contains a corrosion inhibitor or an anti-foaming agent or both, the corrosion inhibitor will not exceed about 1 percent of the composition, and the anti-foaming agent will not exceed about 0.5 percent by weight of the composition, both replacing equivalent amounts of the inert extender.

(B) High strength compositions and aqueous suspension concentrates High-strength compositions generally consist of 90 to 99.5% active ingredient and 0.5 to of a liquid or solid surfactant such as those described in Detergents and Emulsifiers 1968 Annual by J. W. McCutcheon, Inc. Up to approximately half of the surfactant may be replaced by an anti-caking agent such as a synthetic silica. Such high-strength compositions can often be used in a manner similar to the wettable powders but they are also suitable for further formulation.

The aqueous suspension concentrates are prepared by mixing together and sandgrinding an aqueous slurry of water-insoluble active ingredient in the presence of dispersing agents. Thus, there is obtained a concentrated slurry of very finely divided particles in which the active ingredient is substantially all below 5 microns in size. This concentrated aqueous suspension is characterized by its extremely small particle size so that upon diluting and spraying, a very uniform coverage is obtained.

These aqueous suspension concentrates will contain from to 55% of active ingredient, from 40% to 70% water with the remainder made up of surfactants, corrosion inhibitors, and suspending agents.

Suspensions in organic liquids can be prepared in a similar manner such as by replacing the water with mineral oil.

(C) Dusts Dusts are dense powder compositions which are intended for application in dry form and are characterized by their free-flowing and rapid settling properties so that they are not readily windborne to areas where their presence is not desired. They contain primarily an active material and a dense, free-flowing, solid extender.

Their performance is sometimes aided by the inclusion of a wetting agent, and convenience in manufacture frequently demands the inclusion of an inert, absorptive grinding aid. For the dust compositions of this invention, the inert extender may be either of vegetable or mineral origin, the wetting agent is preferably anionic or non-ionic, and suitable absorptive grinding aids are of mineral origin.

Suitable classes of inert solid extenders for use in the dust compositions are those organic or inorganic powders which possess high bulk density and are very free-flowing. They are also characterized by possessing relatively low surface areas and are poor in liquid absorption. Suitable classes of grinding aids are natural clays, diatomaceous earths, and synthetic mineral fillers derived from silica or silicate. Among ionic and non-ionic wetting agents, the most suitable are the members of the group known to the art as wetting agents 'and emulsifiers. Although solid agents are preferred because of ease in incorporation some liquid non-ionic agents are also suitable in the dust formulations.

Preferred inert solid extenders for the dusts of this invention are micaceous talce, pyrophyllite, dense kaolin clays, tobacco dust and ground calcium phosphate rock such as that known as Phosphodust.

Preferred grinding aids are attapulgite clay, diatomaceous, silica, synthetic fine silica and synthetic calcium and magnesium silicates. Preferred Wetting agents are those previously described under wettable powder formulations.

The inert solid extenders in the dusts of this invention are usually present in concentrations of from about 30 to weight percent of the total composition. The grinding aid will usually constitute 5 to 50 weight percent of the composition, and the wetting agent will constitute from about 0 to 1.0 weight percent of the composition. Dust compositions can also contain other surfactants such as dispersing agents in concentrations of up to about 0.5 weight percent.

The wettable powders described above can also be used in the preparation of dusts. While such wettable powders could be used directly in dust form, it is more advantageous to dilute them by blending with the dense dust diluent. In this manner, dispersing agents, corrosion inhibitors, and anti-foam agents may also be found as components of a dust.

Thus, the dust compositions of this invention will usually comprise about 5 to 20 weight percent active material, 5 to 50 weight percent absorptive filler, 0 to 1.0 weight percent wetting agent, and about 30 to 90 weight percent dense, free-flowing dust diluent, as these terms are used herein. Such dust formulations can contain, in addition, minor amounts of dispersants, corrosion inhibitors, and anti-foam agents, derived from the wettable powders used to make the dusts.

The following examples illustrate the use of the compounds and compositions of this invention. Unless otherwise stated, parts are parts by weight.

EXAMPLE 15 Percent 5-(3-phenylureido)-l,3-dimethylpynazole 84.0 Attapulgite clay 7.5 Magnesium carbonate 2.0 Sodium lignin sulfonate 1.5 Finely divided synthetic silica 2.0 Sodium alkylnaphthalenesulfonate 3.0

The above ingredients are blended, micropulverized to a particle size essentially below 50 microns and reblended.

One kilogram of 5-(3-phenylureido)-1,3-dimethylpyrazole formulated as above is suspended in 200 liters of water and applied to a hectare of cotton on which the bolls are open and ready to pick. The treatment accomplishes complete defoliation within days and the cotton can then be machine harvested without contamination with trash or without leaf stains. The treatment also pre vents regrowth of the defoliated plants until they are harvested.

EXAMPLE 16 Percent 5-[3-(2-fluorophenyl)ureido]-4-chloro-l,3-dirnethylpyrazole 25.0 Montmorillonite clay 69.0 Finely divided synthetic silica 2.0 Calcium lignin sulfonate 3.0 Dioctyl sodium sulfosuccinate 1.0

The above ingredients are blended and micropulverized to a particle size smaller than 100 microns and then are reblended.

Two kilograms of the above formulation are suspended in 100 liters of water containing 0.5% Tween 20" (polyoxyethylene sorbitan monolaurate). Two weeks before harvest is planned, the formulation is sprayed on a hectare of late sown soybeans that still has green foliage but the pods are full. This treatment defoliates the plants and allows the pods to dry so that they combine easily when harvested.

EXAMPLE 17 Percent 5 [3 (2 fluorophenyl)ureido]-1,3-dimethylpyrazole 95.0 Trimethylnonyloxypolyethoxyethanol 2.0 Finely divided synthetic silica 3.0

The above ingredients are blended, micropulverized to pass a 0.25 mm. screen and reblended. This formulation is suitable for further formulation or can be applied directly.

Two kilograms of 5-[3-(2-fluorophenyl)ureido]-1,3- dimethylpyrazole as formulated above are suspended in 200 liters of water containing 0.5% Triton X-100 wetting agent (octyl phenoxy polyethoxyethanol) and sprayed on a hectare of cotton two weeks before harvest is planned. The treatment causes rapid defoliation of the cotton plants, the bolls dry and the lint is easily picked by machine two weeks after treatment. The treated area yields clean high quality lint.

EXAMPLE 18 Percent 5-(3-cyclohexylureido)-1,4-dimethyl 3 ethylpyrazole 30.0 Calcium lignin sulfonate and wood sugars 15.0 Hydrated attapulgite 1.5 Sodium pentachlorophenate 0.5 Sodium carbonate 1.0

Water 52.0

The above solid ingredients are micropulverized to pass a 0.59 mm. screen, mixed with the water and sand-ground to a particle size essentially below 5 microns.

A suspension containing 4 kilograms of 5-(3-cyclohexylureido)-1,4-din1ethyl-3-ethylpyrazole as formulated above and 150 liters ,of water containing 0.25% Triton B 1956 wetting agent (modified phthalic glycerol alkyd resin) is sprayed on a hectare of dry beans two weeks before harvest is planned. The pods are full and about ready for harvest but not dry. The treatment defoliates the plants and allows the bean pods to dry. When harvested they shell cleanly with a minimum of cracked or lost seed.

EXAMPLE 19 Percent 5-[3 (3,4 dichlorophenyl)ureido] 1 ethyl-3- methyl-4-chloropyrazole 25.0 Heavy aromatic naphtha 65.0 Oil-soluble calcium sulfonate 5.0 Alkyl phenoxypclyethoxy ethanol 5.0

The active compound is micropulverized to pass an 0.59 mm. screen and is then blended with other ingredients and sand-ground to a particle size essentially below 5 microns. The resulting suspension can be emulsitied into water.

Three kilograms of 5-[3-(3,4-dichl0rophenyl)ureido]- 1ethyl-3-methyl 4 chloropyrazole formulated as described above are suspended in 300 liters of water and sprayed on a hectare of soybeans two weeks before harvest is planned. The treatment defoliates the plants and allows the pods to dry. The dry pods combine easily and cleanly and there are a minimum of beans lost in harvesting.

EXAMPLE 20 Percent 5 (3-methyl-3-phenylureido)-3-methylpyrazole 50.0 Kaolinite 47.0 Methylcellulose 1.0 Sodium alkylnaphthalenesulfonate 2.0

The above ingredients are blended, micropulverized to a particle size essentially below 50 microns and reblended.

A suspension containing 2 kilograms of 5-(methyl-3- phenylureido)-3-methylpyrazole and 300 liters of water containing 0.25% Tween 20 wetting agent is prepared. This is sprayed on a hectare of seed alfalfa when the seeds are full but not dry. The treatment defoliates the plants rapidly and makes it possible to harvest the seed with a minimum of loss.

EXAMPLE 21 Percent 5 [3-(3-nitrophenyl)ureido] 1,3 dimethyl-4- chloropyrazole 50.0 Diatomaceous silica 44.5 Sodium lauryl sulfate 2.0 Finely divided synthetic silica 2.0 Partially desulfonated sodium lignin sulfonate 1.5

The above ingredients are blended, air-milled to a particle size essentially less than 20 microns and reblended.

Five kilograms of 5-[3-(3-nitrophenyl)ureido]-1,3-dimethyl-4-chloropyrazole formulated as shown above are suspended in 200 liters of water containing 0.5% Triton X- wetting agent and sprayed on a hectare of cotton three weeks before harvest is planned. The treatment defoliates the cotton and retards regrowth until the crop is harvested. W'hen harvested the crop gives a good yield of clean, unstained, high quality lint.

I claim:

1. A compound having the formula:

R R O H i N N-t ii r R. l 1

wherein R is hydrogen, methyl, ethyl, or phenyl; R is cyclohexyl, or

Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3836350 *Sep 29, 1972Sep 17, 1974Du PontUreidotriazoles as yield increasing agents for crop plants
US3912496 *Jun 27, 1974Oct 14, 1975Du PontUreidotriazoles as cytokinins and plant antisenescence agents
US4124374 *Sep 27, 1976Nov 7, 1978E. I. Du Pont De Nemours And CompanyAlkyl-substituted cycloalkanapyrazole herbicides
US4162913 *Oct 14, 1975Jul 31, 1979American Cyanamid Co.1,2-Dimethyl-3,5-diphenylpyrazolium-2,2-dichloropropionate
US4465685 *Dec 15, 1981Aug 14, 1984Burroughs Wellcome Co.Antiinflammatory pyrazole thioureas
US4496390 *Jul 15, 1982Jan 29, 1985May & Baker LimitedN-Phenylpyrazole derivatives
US4734122 *Jun 11, 1985Mar 29, 1988Bayer AktiengesellschaftSubstituted 5-acylamino-1-phenylpyrazoles composition containing them, and herbicidal method of using them
US4812576 *Mar 16, 1987Mar 14, 1989Agfa-Gevaert AktiengesellschaftImino derivatives of 4-halogen-pyrazolone-5
US6344476May 22, 1998Feb 5, 2002Bayer CorporationInhibition of p38 kinase activity by aryl ureas
US7235576Jan 11, 2002Jun 26, 2007Bayer Pharmaceuticals CorporationOmega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7329670Dec 27, 1999Feb 12, 2008Bayer Pharmaceuticals CorporationInhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas
US7351834Jan 12, 2000Apr 1, 2008Bayer Pharmaceuticals Corporationω-Carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7371763Jun 22, 2005May 13, 2008Bayer Pharmaceuticals CorporationInhibition of raf kinase using quinolyl, isoquinolyl or pyridyl ureas
US7517880Feb 1, 2002Apr 14, 2009Bayer Pharmaceuticals CorporationInhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
US7528255Feb 11, 2002May 5, 2009Bayer Pharmaceuticals CorporationHydroxy, ω-carboxyaryl substituted diphenyl ureas and dirivatives thereof as raf kinase inhibitors
US7625915Jun 26, 2007Dec 1, 2009Bayer Healthcare LlcInhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas
US7678811Jul 10, 2007Mar 16, 2010Bayer Healthcare LlcPyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors
US7838541Feb 11, 2003Nov 23, 2010Bayer Healthcare, LlcAryl ureas with angiogenesis inhibiting activity
US7897623Aug 27, 2007Mar 1, 2011Bayer Healthcare Llcω-carboxyl aryl substituted diphenyl ureas as p38 kinase inhibitors
US7928239Apr 19, 2011Bayer Healthcare LlcInhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
US8071616Dec 6, 2011Bayer Healthcare LlcPyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors
US8076488Dec 13, 2011Bayer Healthcare LlcBicyclic urea derivatives useful in the treatment of cancer and other disorders
US8110587Feb 11, 2003Feb 7, 2012Bayer Healthcare LlcAryl ureas as kinase inhibitors
US8124630Nov 27, 2001Feb 28, 2012Bayer Healthcare Llcω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US8207166Nov 8, 2010Jun 26, 2012Bayer Healthcare LlcSubstituted pyrazolyl urea derivatives useful in the treatment of cancer
US8242147Sep 23, 2010Aug 14, 2012Bayer Healthcare LlcAryl ureas with angiogenisis inhibiting activity
US8618141Jul 18, 2012Dec 31, 2013Bayer Healthcare LlcAryl ureas with angiogenesis inhibiting activity
US8637553Jul 22, 2004Jan 28, 2014Bayer Healthcare LlcFluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions
US8796250May 19, 2004Aug 5, 2014Bayer Healthcare LlcDiaryl ureas for diseases mediated by PDGFR
US8841330Feb 8, 2012Sep 23, 2014Bayer Healthcare LlcOmega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US9181188Feb 3, 2012Nov 10, 2015Bayer Healthcare LlcAryl ureas as kinase inhibitors
US20030181442 *Nov 27, 2001Sep 25, 2003Bayer Corporationomega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US20030207870 *Feb 11, 2003Nov 6, 2003Bayer CorporationAryl ureas with angiogenisis inhibiting activity
US20030216396 *Feb 11, 2003Nov 20, 2003Bayer CorporationPyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors
US20030216446 *Feb 11, 2003Nov 20, 2003Bayer CorporationAryl ureas as kinase inhibitors
US20040023961 *Feb 11, 2003Feb 5, 2004Bayer CorporationAryl ureas with raf kinase and angiogenisis inhibiting activity
US20050038080 *Jul 22, 2004Feb 17, 2005Stephen BoyerFluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions
US20050059703 *May 19, 2004Mar 17, 2005Scott WilhelmDiaryl ureas for diseases mediated by PDGFR
US20050256174 *Jun 10, 2005Nov 17, 2005Wood Jill ERaf kinase inhibitors
US20060019990 *Jun 22, 2005Jan 26, 2006Jacques DumasInhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
US20060247186 *Jul 5, 2006Nov 2, 2006Carter Christopher AAryl urea compounds in combination with other cytostatic or cytotoxic agents for treating human cancers
US20070020704 *May 19, 2004Jan 25, 2007Scott WilhelmDiaryl ureas with kinase inhibiting activity
US20080009527 *Jun 26, 2007Jan 10, 2008Jacques DumasInhibition of raf kinase using aryl and heteroaryl substituted heterocyclic ureas
US20080027061 *Aug 27, 2007Jan 31, 2008Bernd Riedlomega-Carboxy Aryl Substituted Diphenyl Ureas As p38 Kinase Inhibitors
US20080108672 *Jun 25, 2007May 8, 2008Bernd RiedlOmega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors
US20080153823 *Dec 13, 2007Jun 26, 2008Bernd RiedlOmega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors
US20080194580 *Oct 31, 2007Aug 14, 2008Jacques DumasInhibition Of Raf Kinase Using Quinolyl, Isoquinolyl Or Pyridyl Ureas
US20080227828 *Oct 31, 2007Sep 18, 2008Jacques DumasAryl Ureas With Angiogenisis Inhibiting Activity
US20080269265 *Jun 25, 2008Oct 30, 2008Scott MillerInhibition Of Raf Kinase Using Symmetrical And Unsymmetrical Substituted Diphenyl Ureas
US20080300281 *Jul 28, 2008Dec 4, 2008Jacques DumasInhibition of p38 Kinase Activity Using Aryl and Heteroaryl Substituted Heterocyclic Ureas
US20090093526 *Oct 31, 2007Apr 9, 2009Scott MillerInhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
US20100063088 *Nov 17, 2009Mar 11, 2010Wood Jill ERaf Kinase Inhibitors
US20100075971 *Mar 25, 2010Jacques DumasSubstituted pyridine derivatives useful in the treatment of cancer and other disorders
US20100152251 *Jan 25, 2010Jun 17, 2010Jacques DumasPyridine, quinoline, and isoquinoline n-oxides as kinase inhibitors
US20100160371 *Nov 17, 2009Jun 24, 2010Gerald RangesInhibition of p38 kinase activity by aryl ureas
US20110015195 *Sep 23, 2010Jan 20, 2011Jacques DumasAryl ureas with angiogenisis inhibiting activity
US20110136809 *Nov 8, 2010Jun 9, 2011Bayer Pharmaceuticals CorporationSubstituted Pyrazolyl Urea Derivatives Useful In The Treatment Of Cancer
EP0171544A1 *Jun 19, 1985Feb 19, 1986Bayer AgSubstituted 5-acylamino-1-phenylpyrazoles
EP1041982A1 *Dec 22, 1998Oct 11, 2000Bayer CorporationINHIBITION OF p38 KINASE ACTIVITY USING SUBSTITUTED HETEROCYCLIC UREAS
EP1202734A1 *Aug 11, 2000May 8, 2002PHARMACIA & UPJOHN COMPANY3(5)-ureido-pyrazole derivatives, process for their preparation and their use as antitumor agents
Classifications
U.S. Classification548/371.7, 504/181, 558/452, 558/360, 504/216, 504/169
International ClassificationC07D231/38, C07D231/40
Cooperative ClassificationC07D231/38, C07D231/40
European ClassificationC07D231/40, C07D231/38